{"title":"Supplemental Magnesium Gluconate Enhances Scaffold-Mediated New Bone Formation and Natural Bone Healing by Angiogenic- and Wnt Signal-Associated Osteogenic Activation","authors":"Govinda Bhattarai, Saroj Kumar Shrestha, Shankar Rijal, Sung-Ho Kook, Jeong-Chae Lee","doi":"10.1002/jbm.a.37812","DOIUrl":"10.1002/jbm.a.37812","url":null,"abstract":"<div>\u0000 \u0000 <p>Local implantation or supplementation of magnesium gluconate (MgG) is being investigated as an effective approach to bone repair. Although studies have highlighted the possible mechanisms in Mg ion-stimulated new bone formation, the role of MgG in healing bone defects and the signaling mechanisms are not yet completely understood. In this study, we explored how supplemental MgG has bone-specific beneficial effects by delivering MgG locally and orally in animal models. We fabricated MgG-incorporated (CMC-M) and -free chitosan (CMC) scaffolds with good microstructures and biocompatible properties. Implantation with CMC-M enhanced bone healing in rat model of mandible defects, compared with CMC, by activating Wnt signals and Wnt-related osteogenic and angiogenic molecules. Oral supplementation with MgG also stimulated bone healing in mouse model of femoral defects along with the increases in Wnt3a and angiogenic and osteogenic factors. Supplemental MgG did not alter nature bone accrual and bone marrow (BM) microenvironment in adult mouse model, but enhanced the functioning of BM stromal cells (BMSCs). Furthermore, MgG directly stimulated the induction of Wnt signaling-, angiogenesis-, and osteogenesis-related molecules in cultures of BMSCs, as well as triggered the migration of endothelial cells. These results suggest that supplemental MgG improves bone repair in a way that is synergistically enhanced by Wnt signal-associated angiogenic and osteogenic molecules. Overall, this study indicates that supplemental MgG might ameliorate oxidative damage in the BM, improve the functionality of BM stem cells, and maintain BM-microenvironmental homeostasis.</p>\u0000 </div>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"113 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142515335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Potential of Aloe Vera in Solution and in Blended Nanofibers Containing Poly (3-Hydroxybutyrate-Co-3-Hydroxyvalerate) as Substrates for Neurite Outgrowth","authors":"María-del-Mar Romero-Alemán, José-Manuel Pérez-Galván, José-Enrique Hernández-Rodríguez, Maximina Monzón-Mayor","doi":"10.1002/jbm.a.37825","DOIUrl":"10.1002/jbm.a.37825","url":null,"abstract":"<p>This pilot study investigated the potential of aloe vera (AV) to promote neurite outgrowth in organotypic dorsal root ganglia (DRG) explants (<i>n</i> = 230) from neonatal rats (<i>n</i> = 15). Using this in vitro model of acute axotomy, we assessed neurite outgrowth exceeding 1.5 times the explant diameter (viable explants) and measured the longest neurite length. These parameters were evaluated under control conditions and in cultures supplemented with commercial AV and four aligned scaffolds: poly-L-lactate (PLLA), polydioxanone (PDS), poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), and blended PHBV/AV. After 6 days of culture, explants were immunostained using neuron-specific marker Tuj1 and Schwann cell marker S100. Measurements were obtained with Image J software and analyzed using Jamovi 2.3. In control and AV dilution media, the study revealed radial tissue growth from the explant body with randomly oriented neurites, whereas in all scaffolds, bidirectional tissue growth occurred parallel to nanofibers. Binomial logistic regression analyses indicated that viable explants were more likely in the control group compared to PDS (<i>p</i> = 0.0042) and PHBV (<i>p</i> < 0.0001), with non-significant differences when compared to AV dilution, PLLA, and PHBV/AV. AV dilution showed a greater association with viable explants than PLLA (<i>p</i> = 0.0459), while non-significant difference was found between AV dilution and PHBV/AV. Additionally, the PHBV/AV scaffold predicted higher odds of viable explants than PLLA (<i>p</i> = 0.0479), PDS (<i>p</i> = 0.0001), and PHBV (<i>p</i> < 0.0001). Groups with similar probabilities of obtaining viable explants (control, AV dilution, and PHBV/AV) exhibited non-significant differences in their longest neurite lengths. In conclusion, control, AV dilution, and PHBV/AV yielded the highest probability of developing viable explants and the longest neurite lengths. This is the first study demonstrating the direct permissiveness of AV for axonal outgrowth. Furthermore, the blended PHBV/AV scaffold showed significant potential as a suitable scaffold for axonal regrowth and Schwann cell migration, ensuring controlled tissue formation for tissue engineering applications.</p>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"113 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbm.a.37825","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142515336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gaby D. Lizana-Vasquez, Shanmathi Ramasubramanian, Amin Davarzani, Dan Cappabianca, Krishanu Saha, Lohitash Karumbaiah, Madeline Torres-Lugo
{"title":"In Vitro Assessment of Thermo-Responsive Scaffold as a 3D Synthetic Matrix for CAR-T Potency Testing Against Glioblastoma Spheroids","authors":"Gaby D. Lizana-Vasquez, Shanmathi Ramasubramanian, Amin Davarzani, Dan Cappabianca, Krishanu Saha, Lohitash Karumbaiah, Madeline Torres-Lugo","doi":"10.1002/jbm.a.37823","DOIUrl":"10.1002/jbm.a.37823","url":null,"abstract":"<div>\u0000 \u0000 <p>Chimeric antigen receptor (CAR) T cell immunotherapy has demonstrated exceptional efficacy against hematological malignancies, but notably less against solid tumors. To overcome this limitation, it is critical to investigate antitumor CAR-T cell potency in synthetic 3D microenvironments that can simulate the physical barriers presented by solid tumors. The overall goal of this study was the preliminary assessment of a synthetic thermo-responsive material as a substrate for in vitro co-cultures of anti-disialoganglioside (GD2) CAR-T cells and patient-derived glioblastoma (GBM) spheroids. Independent co-culture experiments demonstrated that the encapsulation process did not adversely affect the cell cycle progression of glioma stem cells (GSCs) or CAR-T cells. GSC spheroids grew over time within the terpolymer scaffold, when seeded in the same ratio as the suspension control. Co-cultures of CAR-T cells in suspension with hydrogel-encapsulated GSC spheroids demonstrated that CAR-T cells could migrate through the hydrogel and target the encapsulated GSC spheroids. CAR-T cells killed approximately 80% of encapsulated GSCs, while maintaining effective CD4:CD8 T cell ratios and secreting inflammatory cytokines after interacting with GD2-expressing GSCs. Importantly, the scaffolds also facilitated cell harvesting for downstream cellular analysis. This study demonstrated that a synthetic 3D terpolymer hydrogel can serve as an artificial scaffold to investigate cellular immunotherapeutic potency against solid tumors.</p>\u0000 </div>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"113 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142515334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Benedict Rothammer, Klara Feile, Siegfried Werner, Rainer Frank, Marcel Bartz, Sandro Wartzack, Dirk W. Schubert, Dietmar Drummer, Rainer Detsch, Bo Wang, Andreas Rosenkranz, Max Marian
{"title":"Ti3C2T\u0000 x-UHMWPE Nanocomposites—Towards an Enhanced Wear-Resistance of Biomedical Implants","authors":"Benedict Rothammer, Klara Feile, Siegfried Werner, Rainer Frank, Marcel Bartz, Sandro Wartzack, Dirk W. Schubert, Dietmar Drummer, Rainer Detsch, Bo Wang, Andreas Rosenkranz, Max Marian","doi":"10.1002/jbm.a.37819","DOIUrl":"10.1002/jbm.a.37819","url":null,"abstract":"<p>There is an urgent need to enhance the mechanical and biotribological performance of polymeric materials utilized in biomedical devices such as load-bearing artificial joints, notably ultrahigh molecular weight polyethylene (UHMWPE). While two-dimensional (2D) materials like graphene, graphene oxide (GO), reduced GO, or hexagonal boron nitride (h-BN) have shown promise as reinforcement phases in polymer matrix composites (PMCs), the potential of MXenes, known for their chemical inertness, mechanical robustness, and wear-resistance, remains largely unexplored in biotribology. This study aims to address this gap by fabricating Ti<sub>3</sub>C<sub>2</sub>T<sub>\u0000 <i>x</i>\u0000 </sub>-UHMWPE nanocomposites using compression molding. Primary objectives include enhancements in mechanical properties, biocompatibility, and biotribological performance, particularly in terms of friction and wear resistance in cobalt chromium alloy pin-on-UHMWPE disk experiments lubricated by artificial synovial fluid. Thereby, no substantial changes in the indentation hardness or the elastic modulus are observed, while the analysis of the resulting wettability and surface tension as well as indirect and direct in vitro evaluation do not point towards cytotoxicity. Most importantly, Ti<sub>3</sub>C<sub>2</sub>T<sub>\u0000 <i>x</i>\u0000 </sub>-reinforced PMCs substantially reduce friction and wear by up to 19% and 44%, respectively, which was attributed to the formation of an easy-to-shear transfer film.</p>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"113 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbm.a.37819","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142515337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}